In this thesis the existence and possible importance of any gradients in the basolateral
potassium (K+) currents of adult mammalian inner hair cells (mCs) were investigated.
Gradients in three K currents, the linopirdine sensitive current IK,n, a fast activating
current IK,f' and a delayed rectifying current IK,s, were compared in three animal species,
together with voltage responses and exocytosis as a proxy to neurotransmitter release.
In gerbil IRCs IK,n increased towards the basal, high-frequency region, whereas in
guinea-pigs and mice no gradient was observed. The hypothesized IK,n channel subunit
KCNQ4 was transiently or stably transfected into cell lines. The current recorded from
the transient transfections suggested KCNQ4 is indeed a good candidate for IK,n.
However as the current changed characteristics after multiple passages ofthe cells it was
concluded that a secondary intracellular factor may be required for the current to
activate over the very negative range at which IK,n is active in the hair cells.
IK,s was shown to increase tonotopically toward the high-frequency IRCs in the gerbil.
This expression opposes the' gradient of IK,s in the guinea-pig. The expression of IK,f in
the gerbil also differed from the guinea-pig. To compare how the various tonotopic
gradients influence the membrane potential, membrane voltage were recorded in
response to current injection. Comparisons were also made between exocytosis in the
apical and basal mcs. In both gerbil and guinea-pig no difference was apparent in the
voltage dependence of capacitance or calcium current between apical and basal mcs.
Having established the normal physiological properties, the same techniques were used
to study mature IHCs of the mouse mutant Snell's waltzer that lacks myosin VI, leading
to recessive deafuess and vestibular defects. The mcs ofthese mice were found to have
no IK,f or IK,n and current injection induced spike-like responses, indicating a defect in
maturation. In addition, exocytosis was greatly reduced in homozygous mutants,
suggestive of an involvement ofmyosin VI in exocytosis.
In conclusion, no clear generally applicable role has emerged from the data in this thesis for
tonotopic gradients of basolateral K+ currents in mammalian inner hair cells. However the
presence and direction of tonotopic gradients, different in different species, is intriguing and
merits further investigation.